The primary objective of this research program involves the synthesis of new folate analogs directed toward improved chemotherapy of colon adenocarcinoma. The compounds to be prepared will consist largely of quinazoline derivatives of naturally occurring folates and known folic acid antagonists. Most of the target compounds will be prepared on a micro scale, purified if necessary by high-speed liquid chromatography, and then forwarded to Dr. Joseph Bertino for in vitro evaluation. Results obtained from tissue culture and enzyme inhibition studies will determine whether larger quantities will be prepared for in vivo antitumor testing and will also help to direct future synthetic efforts. The chemistry to be performed will involve a continuation and expansion of technology already developed in this laboratory. Particular emphasis will be placed on chemcial modifications of 5,8-dideazaisofolic acid, IAHQ, a compound having potential in the treatment of colon tumors. Derivatives which may enhance delivery to target cells, alter metabolic degradation, and/or reduce host toxicity will receive priority. Poly-Gamma-L-glutamyl derivatives of active compounds will also be prepared for mechanistic studies.